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Membrane remodeling by the PX-BAR protein SNX18 promotes autophagosome formation
- Source :
- The Journal of Cell Biology
- Publication Year :
- 2013
- Publisher :
- Rockefeller University Press, 2013.
-
Abstract
- SNX18 promotes autophagosome formation by remodeling membranes and providing membrane to forming autophagosomes.<br />The membrane remodeling events required for autophagosome biogenesis are still poorly understood. Because PX domain proteins mediate membrane remodeling and trafficking, we conducted an imaging-based siRNA screen for autophagosome formation targeting human PX proteins. The PX-BAR protein SNX18 was identified as a positive regulator of autophagosome formation, and its Drosophila melanogaster homologue SH3PX1 was found to be required for efficient autophagosome formation in the larval fat body. We show that SNX18 is required for recruitment of Atg16L1-positive recycling endosomes to a perinuclear area and for delivery of Atg16L1- and LC3-positive membranes to autophagosome precursors. We identify a direct interaction of SNX18 with LC3 and show that the pro-autophagic activity of SNX18 depends on its membrane binding and tubulation capacity. We also show that the function of SNX18 in membrane tubulation and autophagy is negatively regulated by phosphorylation of S233. We conclude that SNX18 promotes autophagosome formation by virtue of its ability to remodel membranes and provide membrane to forming autophagosomes.
- Subjects :
- Autophagosome
Endosome
education
Fat Body
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Autophagy-Related Proteins
Endosomes
Biology
Article
Cell membrane
03 medical and health sciences
0302 clinical medicine
Phagosomes
Protein Interaction Mapping
Autophagy
medicine
Animals
Drosophila Proteins
Humans
Phosphorylation
RNA, Small Interfering
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Sorting Nexins
Research Articles
030304 developmental biology
Phagosome
0303 health sciences
Membrane tubulation
Cell Membrane
Intracellular Signaling Peptides and Proteins
Cell Biology
PX domain
Transport protein
Cell biology
Protein Transport
HEK293 Cells
medicine.anatomical_structure
Larva
Proteolysis
Drosophila
Carrier Proteins
Microtubule-Associated Proteins
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15408140 and 00219525
- Volume :
- 202
- Database :
- OpenAIRE
- Journal :
- Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....bf59b16d5c81660476b9a174ec39b00b